Puncturable and resealable graft

ABSTRACT

Implantable grafts, particularly for arteriovenous access that may be punctured by an object such as a needle and, following removal of the object, will reseal the resulting hole to the extent of reducing fluid leakage through the graft at the puncture site to an amount less than would be typical for a conventional graft. More particularly, the grafts comprise three layers; an inner layer of implantable graft material such as ePTFE, a middle layer of self sealing elastomeric material such as silicone, and an outer layer of implantable graft material such as ePTFE. Following manufacture, the tubular form of the three-layer graft is everted to put substantially the entire wall thickness of the elastomeric material layer under circumferential compression.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.15/364,524, filed Nov. 30, 2016, entitled PUNCTURABLE AND RESEALABLEGRAFT, which is a continuation of U.S. application Ser. No. 13/644,160,filed Oct. 3, 2012, entitled PUNCTURABLE AND RESEALABLE GRAFT, now U.S.Pat. No. 9,539,360, issued Jan. 10, 2017, which claims priority to U.S.Provisional Application Ser. No. 61/545,044 filed Oct. 7, 2011, entitledPUNCTURABLE AND RESEALABLE GRAFT, all of which are herein incorporatedby reference in their entireties.

FIELD OF THE INVENTION

The present invention relates to the field of implantable grafts,particularly grafts for arteriovenous access, that may be punctured byan object such as a needle and, following removal of the object, willreseal the resulting hole to the extent of reducing fluid leakagethrough the graft at the puncture site to an amount less than would betypical for a graft.

BACKGROUND OF THE INVENTION

Various grafts have been described in the literature that have attemptedto offer solutions to the problem of reducing leakage of fluids frompuncture sites following removal of the puncturing object. Typical graftmaterials for these grafts, which are most typically grafts intended forarteriovenous access wherein the graft may be pierced repeatedly, atintervals, by dialysis needles, are polyethylene terephthalate (PET) andexpanded polytetrafluoroethylene (ePTFE). These grafts are typicallytubular grafts, although planar sheet grafts, often for use in patchinga portion of the surface of a tube, are also known.

A construction that has been described previously in various forms forreduced leakage involves the use of laminates of the above materialswith a layer of a self-sealing material such as an implantableelastomeric material. These elastomeric materials are typicallysilicone, polyurethane or fluoroelastomers. The use of one layer ofgraft material joined to one layer of elastomeric material has beendescribed, although the most frequently described laminates involve alayer of the elastomeric material that is covered on both surfaces(e.g., inner and outer surfaces) by a layer of the graft material. Thelayers of graft material may be the same or may be different materialson the two surfaces; the graft materials may also differ in thickness,bulk density, porosity, orientation or other attributes even if they areessentially of the same chemical makeup.

A particular variation of these laminates, particularly for tubularconstructions, involves the use of a tubular elastomeric materialcomponent that has been everted (i.e., turned inside out) prior tolaminating this tube to one or more layers of graft material). Theeverted tube of elastomeric material is under circumferentialcompression at its luminal surface while the abluminal surface is undercircumferential tension.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A describes a transverse cross section of one embodiment of thegraft described herein as manufactured on a cylindrical mandrel.

FIG. 1B shows a transverse cross section of the graft shown in FIG. 1Aafter it has been removed from the mandrel and everted by turning thetube of FIG. 1A inside out.

SUMMARY OF THE INVENTION

Implantable grafts are described, particularly grafts for arteriovenousaccess that may be punctured by an object such as a needle and,following removal of the object, will reseal the resulting hole to theextent of reducing fluid leakage through the graft at the puncture siteto an amount less than would be typical for a graft. More particularly,the grafts comprise three layers; an inner layer of implantable graftmaterial such as ePTFE, a middle layer of self sealing elastomericmaterial such as silicone, and an outer layer of implantable graftmaterial such as ePTFE. Following manufacture, as will be furtherdescribed, the tubular form of the three-layer graft is everted to putsubstantially the entire wall thickness of the elastomeric materiallayer under circumferential compression.

The outer layer of graft material (the inner layer prior to everting thetube) is a high tensile strength material with the high strengthdirection oriented circumferentially about the tubular graft. Thestrength of the graft material may be appreciably less in thelongitudinal direction of the tubular graft. One such material is ePTFEfilm that has been cut into a tape of greater length than width and withthe high strength direction parallel to the length of the tape. Thistape is used to create a helical winding that constitutes an outersurface of the completed (post-eversion) tubular graft.

The graft may be made by helically wrapping the ePTFE tape about thesurface of a mandrel. The films from which the tapes are cut aregenerally described by U.S. Pat. No. 3,953,566, incorporated byreference herein. Preferred films have high strength in one directionwhich is the direction of fibrillar orientation for uniaxial films, withthe fibrils oriented to be substantially parallel to the length of ePTFEtapes cut from such films. The helical wrapping may be in a singledirection along the length of the chosen mandrel, with the result thatthe strength direction of the wrapping is substantially in thecircumferential direction as opposed to the longitudinal direction. Inanother embodiment the helical wrapping may be performed in both in bothdirections along the length. In another embodiment, multiple wrappingpasses along the mandrel length may be made if desired.

Following completion of the helically wrapped film layer, the layer ofelastomeric material is provided. Silicone of selected durometer may beused in one embodiment; in other embodiments polyurethanes may be used.Still another embodiment provides a fluoroelastomer for this layer suchas a copolymer of tetrafluoroethylene and a polyalkylvinylether(TFE/PAVE); one such is a copolymer of TFE and polymethylvinylether(TFE/PMVE). These materials are taught by U.S. Pat. No. 7,049,380 and US2006/00198866, incorporated by reference herein. The elastomericmaterial may be applied over helically-wrapped films by various methods,including the use of pre-formed tubes of the elastomeric material oralternatively the material may be applied in an uncured form over thehelically wrapped film, such as by dip coating or spray coating. Some ofthese methods are taught by U.S. Pat. No. 8,029,563, also incorporatedby reference herein. The elastomeric material may be cured or partiallycured following application.

Additionally, combinations of the above-mentioned elastomers are alsocontemplated. For example, a layer of fluoroelastomer (e.g., TFE/PMVEcopolymer) may be applied over a vascular graft substrate tube andallowed to dry, followed by an additional layer of silicone. Likewise,the inner/outer relationship of the two different elastomers may bereversed. Also, combinations of the same type of elastomers havingdifferent forms may be applied, such as an inner layer of silicone maybe applied first over the vascular graft substrate tube followed by asecond layer of silicone that is an uncured layer. In this fashion, onelayer of cross-linked elastomer provides the necessary force to compressand seal a needle puncture site while the second outer layer ofelastomer (which may also be a partially cured layer of the same type ofelastomer) that, in use, may be expected to flow and “heal” the puncturesite following needle removal. It is apparent that the relationships ofinner and outer layers as described during construction will be reversedfollowing eversion of the constructed tubular form (as will be describedbelow) to result in a finished tubular graft available for use(following the necessary step of sterilization by suitable means) as avascular graft intended for dialysis applications.

Finally, an additional layer of graft material (e.g., PET or ePTFE) isapplied over the elastomeric material. In one embodiment this is ePTFEand more particularly may be a longitudinally extruded and expanded tubeof ePTFE. In one embodiment this tube has a wall thickness of about 0.1mm and a mean fibril length of about 25-35 microns. It is apparent thatthese dimensions may be varied as desired. Alternatively, this layer maybe made of helically wrapped ePTFE film. This graft layer of graftmaterial may be joined to the underlying layer of elastomeric materialby an adhesive such as an implantable silicone medical adhesive, or bycuring the underlying elastomeric material after the outer graftmaterial is provided.

It is further apparent that the graft layers may also include additionalelastomeric materials so long as the intermediate elastomeric materiallayer described above is included.

Following completion of the above-described three layers including theintermediate layer of elastomeric material with both sides covered withgraft material, the resulting tubular graft material is removed from themandrel. In one embodiment, this removal is accomplished by everting thetubing back over itself and removing it from the mandrel during theprocess of eversion. Alternatively, the tubular construct may be evertedafter removal from the mandrel.

The layer of helically wrapped graft material with the predominantstrength direction oriented substantially circumferentially has adiameter that is substantially unchanged by the step of everting thetube. The materials that were provided over the helically wrapped layerwhile still on the manufacturing mandrel become circumferentiallycompressed during eversion of the tube wherein the elastomeric materiallayer in particular is reduced in diameter and remains in a state ofcircumferential compression that aids significantly in reducing puncturesite leakage of the resulting graft. This is anticipated to be ofparticular use for vascular grafts intended for dialysis, possiblein-situ fenestration for side branch endoprosthesis placement, and issimilarly useful for grafts that have been punctured by suture needles.

An indication of the elastomeric material layer being in a state ofcircumferential compression through substantially its entire wallthickness may be seen by taking a length of the everted tube made asdescribed above and cutting it through the wall in a longitudinaldirection, parallel to the longitudinal axis of the tube. After beingcut through, the resulting sheet will curl in a direction opposite tothe curvature of the original everted tube, i.e., the outer surface ofthe curled sheet will have previously been the luminal surface of theeverted tube.

Additionally, a completed implantable vascular graft made generally asdescribed above (e.g., including the step of eversion following removalfrom the mandrel on which it was constructed) has a tubular structurewith a first outside diameter wherein, when that tubular structure iseverted, has a second outside diameter that is larger than the firstoutside diameter. This eversion to the second larger outside diameter,is in effect a second eversion back to its condition as manufactured onthe mandrel prior to: removal from the mandrel and the first eversionduring manufacture. The second outside diameter is typically larger thanthe first outside diameter by an amount that is equal to at least thewall thickness of the tubular structure.

Wall thickness is preferably measured by fitting the tubular structureover a mandrel that is a snug fit to the inside diameter of the tubularstructure, the snug fit requiring a small force to fit the tube over themandrel surface. The use of substantial force to fit the tube to themandrel may result in an undesired increase of the outside diameter ofthe tube. When fitted over a mandrel of appropriate diameter, theoutside diameter of the tube may be measured with a suitable lasermicrometer. The wall thickness is the indicated outside diameter of thetube minus the mandrel diameter, divided by two. At least threemeasurements should be made at different locations along the length ofthe tube, the wall thickness being the average of the threemeasurements.

The graft may also be provided in planar form. In one embodiment thismay be accomplished simply by cutting a tube made as described abovealong its length.

Other methods for applying compressive stresses to the elastomer arealso envisioned. One method involves the fabrication of one component asa composite tube having an ePTFE liner and cured or semi-cured coatingof silicone, a second component being an ePTFE tube having significantradial strength and fabricated at a slightly smaller diameter than thefirst component, and then placing the first component into the secondcomponent. The components may be slipped together where interference fitholds them in place or, they may be fitted together and adhered in placeby using a thin coating of silicone adhesive prior to fitting the twotubes together. In either case, the ePTFE tube of component two willhold the composite tube of component one at a smaller size thanoriginally fabricate, resulting in residual compressive stressesthroughout the thickness of the elastomeric layer. Component two may beprovided with a stent component if desired, thereby creating astent-graft

Utilizing residual compressive stresses within the elastomer, thepuncture tolerance of the present invention is increased dramatically.This increase in tolerance allows for reduced graft wall thickness incomparison to prior devices while still providing effective leakresistance. This reduction in thickness has provided for the fabricationof a true endoluminal graft or stent-graft that may be diametricallycompacted to an appropriate insertion profile and mounted upon or withina delivery system for subsequent deployment at a desired site to itslarger diameter.

The stent structure may be provided to at least a portion of the lengthof the tubular graft material. The stent structure may be self-expandingor may be balloon expandable. The balloon expandable stents may bemachined from a plastically deformable metal such as any of variousimplantable stainless steels. Self-expanding stents may be made ofnitinol and more particularly made of nitinol wire. One such embodimentuses nitinol wire that has been helically wound into a generally tubularform; a variation of this embodiment uses wire that has been bent into aserpentine pattern with alternating apices directed in opposingdirections, and then this serpentine wire is helically wound into thegenerally tubular shape; see, for example, U.S. Pat. No. 6,551,350,incorporated by reference herein. The stent structure may be provided onthe outer surface of the above-described tubular graft in oneembodiment. In another embodiment the stent may be provided on the innersurface of the graft and in another embodiment the stent structure maybe incorporated into the wall thickness of the graft. In anotherembodiment the stent structure may be provided at one or both ends ofthe graft as generally taught by US 2007/0198077 and US 2007/0076587.

DETAILED DESCRIPTION OF THE DRAWINGS

FIG. 1A describes a transverse cross section of one embodiment of thegraft described herein as manufactured on a cylindrical mandrel whileFIG. 1B shows the same graft after it has been removed from the mandreland everted by turning the tube of FIG. 1A inside out. As shown by FIG.1A, mandrel 18 is provided with a covering 12 of a graft material havinga high circumferential strength, such as a helical wrapping of a thinePTFE tape having a uniaxial microstructure with the strength directionof the tape parallel to the length of the tape whereby circumferentialstrength is provided when the mandrel is helically wrapped with such atape. Next, one or more layers of an elastomeric material 14 areprovided over the helical wrapping of tape 12, after which anothercovering 16 of graft material is provided over the elastomeric material14. In one embodiment this covering 16 is porous ePTFE and may be alongitudinally extruded and expanded ePTFE tube or alternatively may beprovided as a helical wrapping of ePTFE.

FIG. 1B is a transverse cross section of the tube of FIG. 1A followingremoval of the mandrel 18 and following eversion of the composite tube,resulting in implantable tubular vascular graft 10. It is noteworthythat the outside diameter “D” of graft 10 is substantially the same asthe outside diameter of covering 12 as laid up on mandrel 18 shown inFIG. 1A prior to eversion. Elastomeric material layer 14 of implantabletubular vascular graft is now circumferentially compressed andconstrained by cover 12 following eversion as shown in FIG. 1B. It isnoteworthy that substantially the entire thickness of the elastomericlayer is under circumferential compression which in combination with thematerial properties of the elastomeric material chosen provides graft 10with its self-sealing capability. The outer portion of the wallthickness of the layer of elastomeric material is under the least amountof circumferential compression (little or no circumferentialcompression) and the inner portion of the wall thickness of the layer ofelastomeric material is under the greatest amount of circumferentialcompression. It is possible that the wall thickness of this layer ofelastomeric material may slightly increase following eversion. Covering16 is also circumferentially compressed, now providing the luminalsurface of graft 10. The porous material of layer 16, such as an ePTFEtubular structure, easily accommodates this compression withoutappreciable deformation at the luminal surface.

Examples

An ePTFE tape of about 2.5 mm width and about 0.0025 mm thickness wasobtained, the tape having a substantially uniaxial fibrillarmicrostructure with a matrix tensile strength of about 26000 psi (180MPa) in the high strength direction (along the length) of the tape. Thismaterial had a bulk density of about 0.6 g/cc, in comparison to thedensity of non-porous PTFE of about 2.2 g/cc. A stainless steel mandrelof about 8 mm diameter was obtained and provided with a tubular coveringof a longitudinally extruded and expanded ePTFE (thickness about 0.25mm). A helical wrapping of the obtained tape was applied by wrapping thetape over the covered mandrel in one direction only with a resultingthickness of 5 layers of the tape along the length of the resultingtube. The assembly was placed into a convection oven set at 370° C. for10 minutes, after which time it was removed from the oven and allowed tocool. The mandrel was removed and replaced with another of the same sizethat had been provided with a surface covering of a release material(e.g., Kapton). The ePTFE tube was then provided with a coating of NusilMED-1137 Silicone (Nusil Technology, Carpenteria Calif. 93013) which wassmoothed manually. Before the silicone cured to the point of hardeningit was then helically wrapped in three passes (in alternatingdirections) with another 5 layers of the same film per pass (total 15layers). This was followed by another application of silicone and withanother 5 layers of film helically wrapped in one direction. Theassembly was placed into an oven set at 65° C. for 20 or more hours tocure the silicone. A container of de-ionized water was placed into theoven during this time to assist in the curing process. After completionof this time the assembly was removed from the oven and the mandrel wasremoved from the tubular construct, after which the tubular constructwas everted to create the tubular graft.

The resulting graft had a total wall thickness of about 0.38 mm. It wastested by pressurizing with room temperature water at 2.5 psi (17.2KPa), and then inserting a new 16 gauge dialysis needle through the wallof the graft at an angle of about 45 degrees, with the beveled surfaceof the needle facing up. When the needle was removed from thepressurized graft there was a small stream of water from the puncturesite that lasted about two seconds, after which a droplet of waterformed momentarily at the puncture site. Leakage of the pressurizedgraft then stopped entirely.

Another graft was made with the same process, using a slightly lesseramount of silicone with a resulting wall thickness of about 0.33 mm.This graft, after fitting over a stainless steel mandrel, was providedwith a helically wrapped covering of a TFE/PMVE fluoroelastomer tape(material made according to U.S. Pat. No. 7,049,380) of 2.5 cm width,applied at a pitch that resulted in a 3 layer thick application of thistape. Another 5 layers of the above-described ePTFE tape was wrappedaround the outer surface to secure the fluoroelastomer and to cause itto flow to create a uniform thin covering. This construct was placedinto a convection oven set at 220° C. for 15 minutes, then removed andallowed to cool, after which the mandrel was removed. The resultinggraft, after eversion, had a wall thickness of about 0.41 mm. Whenpressure tested as described above, when the dialysis needle was removeda water droplet formed momentarily at the puncture site, immediatelyafter which all leakage stopped.

The outer surface of a length of graft made as described above usingonly silicone as the elastomeric material was fitted with a nitinolserpentine wire stent (wire diameter about 0.2 mm). The stent wasadhered to the outer surface of the stent using the TFE/PMVEfluoroelastomer described above as a melt-bond adhesive. The stent wasmade generally as described for the stent-graft portion of the devicedescribed in U.S. Pat. No. 6,673,102, incorporated by reference herein.The resulting stent-graft was compacted to a diameter of about 13 French(about 4.3 mm) using a funnel-type compactor as described in U.S. Pat.No. 6,673,102. This demonstrates that such a stent-graft may beimplanted and deployed endoluminally.

In addition to being directed to the teachings described above andclaimed below, devices and/or methods having different combinations ofthe features described above and claimed below are contemplated. Assuch, the description is also directed to other devices and/or methodshaving any other possible combination of the dependent features claimedbelow.

Numerous characteristics and advantages have been set forth in thepreceding description, including various alternatives together withdetails of the structure and function of the devices and/or methods. Thedisclosure is intended as illustrative only and as such is not intendedto be exhaustive. It will be evident to those skilled in the art thatvarious modifications may be made, especially in matters of structure,materials, elements, components, shape, size and arrangement of partsincluding combinations within the principles of the invention, to thefull extent indicated by the broad, general meaning of the terms inwhich the appended claims are expressed. To the extent that thesevarious modifications do not depart from the spirit and scope of theappended claims, they are intended to be encompassed therein.

We claim:
 1. An implantable device comprising a tubular structureincluding a first layer, a second layer, and an elastomeric layerbetween the first and second layers, an entire thickness of which isunder circumferential compression following eversion of the tubularstructure, the tubular structure having a first outside diameter priorto eversion, wherein when everted the tubular structure has a secondoutside diameter that is larger than the first outside diameter, andwherein the tubular structure has a wall thickness and the secondoutside diameter is larger than the first outside diameter by an amountthat is equal to or greater than the wall thickness.
 2. The implantabledevice of claim 1, wherein the implantable device is a vascular graft.3. The implantable device of claim 1, wherein each of the first andsecond layers of the tubular structure include graft layers formed ofePTFE.
 4. The implantable device of claim 1, wherein the elastomericlayer includes silicone.
 5. The implantable device of claim 1, whereinthe elastomeric layer includes a fluoroelastomer.
 6. The implantabledevice of claim 1, wherein the elastomeric layer includes a copolymer oftetrafluoroethylene and polyalkylvinylether.
 7. The implantable deviceof claim 1, wherein the elastomeric layer is a polyurethane.
 8. Theimplantable device of claim 1, wherein the elastomeric layer comprisestwo layers of different elastomers.
 9. The implantable device of claim1, wherein the elastomeric layer comprises a silicone and afluoroelastomer.
 10. The implantable device of claim 1, wherein theelastomeric layer comprises an outer layer of fluoroelastomer and aninner layer of silicone.
 11. The implantable device of claim 1, whereinthe elastomeric layer comprise an inner layer of fluoroelastomer and anouter layer of silicone.
 12. The implantable device of claim 1, whereinthe tubular structure has a first, larger outside diameter and a firstlarger inside diameter prior to eversion, and a second, smaller outsidediameter and a second smaller inside diameter following eversion,wherein the difference between the first outside diameter and the secondoutside diameter is greater than the difference between the first insidediameter and the second outside diameter.
 13. An implantable vasculargraft comprising a tubular structure having a first outside diameterwherein, when everted, has a second outside diameter that is larger thanthe first outside diameter, the tubular structure including inner andouter layers of a graft material and an intermediate layer of anelastomeric material, where substantially the entire thickness of theelastomeric layer is under circumferential compression from the graftmaterial prior to eversion of the implantable tubular vascular graft.14. The implantable vascular graft of claim 13, wherein the tubularstructure has a wall thickness and the second outside diameter is largerthan the first outside diameter by an amount that is equal to at leastthe wall thickness.
 15. The implantable vascular graft of claim 13,wherein the elastomeric material adheres the inner layer of the graftmaterial to the outer layer of the graft material.
 16. The implantablevascular graft of claim 13, wherein the inner layer of graft materialhas a high strength direction oriented circumferentially about thetubular structure relative to the strength direction oriented in alongitudinal direction of the tubular structure.
 17. The implantablevascular graft of claim 13, wherein the inner layer of graft material iscomprised of helically wrapped film tape.
 18. The implantable vasculargraft of claim 13, wherein the inner layer of graft material iscomprised of a uniaxial film.
 19. The implantable vascular graft ofclaim 13, wherein the outer layer of graft material is comprised of alongitudinally extruded and expanded tube of ePTFE.
 20. The implantablevascular graft of claim 13, wherein the outer layer of graft material iscomprised of helically wrapped ePTFE film.